Effects of green light-emitting diode irradiation on neural differentiation of human umbilical cord matrix-derived mesenchymal cells; Involvement of MAPK pathway

Abstract

Alteration of the proliferation rate and differentiation of mesenchymal stem cells (MSCs) into various lineages, including neural cells, by light emitting diodes (LEDs) irradiation has received considerable attention in recent years. Human umbilical cord matrix-derived mesenchymal cells (hUCMs) are an accessible source of adult stem cells with appropriate characteristics that make them ideal tools for stem cell researches, cell therapy procedures and regenerative medicine. The aim of the present study was to investigate the effects of green LED irradiation, retinoic acid (RA) and their combination on the differentiation of hUCMs into neural lineage as well as the mechanisms involved. Exposure of hUCMs to green LED (530 nm, 1.59 J/cm2) with or without retinoic acid (RA) treatment, significantly increased the expression of specific genes including nestin, β-tubulin III, MAP2 and Olig2. In addition, immunohistochemical analysis confirmed expression of specific neural-related proteins including MAP2, GFAP and Olig2 in irradiated cells. ROS generation significantly increased following green light irradiation which in turn has activated the MAPK signaling pathway, resulting in the differentiation of hUCMs into neurons and glial cells, confirmed by western blot analysis of MAPK-related pathway. Taken together, our results suggest that the green LED irradiation, alone and in combination with RA, via ERK 1/2, JNK and p38 phosphorylation improves differentiation of hUCMs into neural lineage. Other mechanisms and inducers to enhance differentiation phenomena in vitro and in vivo should be investigated to determine the most appropriate strategy for therapeutic purposes.